1. Field of the Invention
The present invention is directed to flow cytometers.
2. Description of the Related Art
Flow cytometers are useful in the detection of particulates in liquid systems, in particular for the detection and/or identification of microbes, including pathogens. Flow cytometry per se is a mature technology. Flow cytometers concentrate a particulate-containing inlet stream to a relatively small diameter “observation” stream in which the particles pass “single file” past a detector located in an observation channel. Focusing of the liquid sample is achieved by injecting a liquid as a sheath surrounding the stream of sample. The necessity for a rather large volume of liquid relative to the volume of sample contributes to the overall size of the device, and with biological samples suspected of containing pathogens, contributes to waste disposal problems. Reducing complexity by eliminating liquid focusing has been attempted, J. Crosland-Taylor, NATURE 171, 37-38 (1953), but has not been regarded as successful, due to deficiencies such as channel clogging and slow velocity of sample flow which reduces the optical detection rate. Thus, current flow cytometers employ liquid focusing.
Typical flow cytometers are bench scale devices comprising a flow cytometer cell, a laser light source, and a photomultiplier detector. In order to produce an acceptable signal to noise ratio, the detection system also includes a dichroic beam splitter, focusing optics, and a combination of photodiode and photomultiplier. A typical flow cytometer is represented schematically in FIG. 1. The most compact commercial instruments occupy more than 2 ft3 (ca. 0.07 m3) of space, and are quite expensive. Typical flow cells are constructed of quartz, and alone cost ca. U.S. $3500 (2002) and thus are clearly not disposable. The optical components of the detection system are major contributors to the overall cost, as are the laser and photomultiplier.
Flow cytometers have gained widespread use in a variety of medical, scientific, and engineering fields such as disease diagnosis and monitoring, D. S. Stein et al., J. INFECT. Dis. 165 (2), 352-63 (1992); D. Fenili et al. CLIN. CHEM. LAB. MED., 36 (12), 909-17 (1998), cell biology C. L. Harding, et al., BIOTECHNOL. PROG. 16 (5), 800-02 (2000), toxicology, K. A. Criswell, et al., CYTOMETRY 32 (1), 18-27 (1998), and environmental monitoring, G. B. J. Dubelaar, SCIENTIA MARINA 64 (2), 255-65 (2000). Flow cytometers have been used in monitoring of white blood cells for HIV infection, and for monitoring of dialysis fluids and the like. Use of flow cytometers is also being increasingly investigated in view of threats of biological contamination, not only due to terrorist activities, but also due to increased contamination of water supplies caused by steadily increasing population density.
It would be desirable to provide flow cytometers which occupy less physical space, to the extent, for example, of providing hand held devices. It would further be desirable to provide flow cytometers which do not rely on liquids as the focusing fluid, and which utilize less expensive, and less bulky detection devices. It would be desirable to provide flow cytometer cells which are disposable as a practical matter.